TY - JOUR
T1 - Final results of phase III SYMMETRY study
T2 - Randomized, double-blind trial of elesclomol plus paclitaxel versus paclitaxel alone as treatment for chemotherapy-naive patients with advanced melanoma
AU - O'Day, Steven J.
AU - Eggermont, Alexander M.M.
AU - Chiarion-Sileni, Vanna
AU - Kefford, Richard
AU - Grob, Jean Jacques
AU - Mortier, Laurent
AU - Robert, Caroline
AU - Schachter, Jacob
AU - Testori, Alessandro
AU - Mackiewicz, Jacek
AU - Friedlander, Philip
AU - Garbe, Claus
AU - Ugurel, Selma
AU - Collichio, Frances
AU - Guo, Wei
AU - Lufkin, Joelle
AU - Bahcall, Safi
AU - Vukovic, Vojo
AU - Hauschild, Axel
PY - 2013/3/20
Y1 - 2013/3/20
N2 - Purpose: Elesclomol, an investigational first-in-class compound, induces oxidative stress, triggers mitochondrial-induced apoptosis in cancer cells, and shows synergy with taxanes in tumor models. Following completion of a phase II trial of elesclomol in combination with paclitaxel that met its primary end point of progression-free survival (PFS), this randomized, double-blind, controlled phase III study was conducted to confirm the efficacy and tolerability of elesclomol in combination with paclitaxel versus paclitaxel alone in patients with advanced melanoma Patients and Methods: Patients with stage IV chemotherapy-naive melanoma (n = 651) were randomly assigned 1:1 to paclitaxel 80 mg/m2 either alone or in combination with elesclomol 213 mg/m2 administered weekly for 3 weeks of a 4-week cycle. Patients were stratified by prior systemic treatment, M1 subclass, and baseline lactate dehydrogenase (LDH) levels. The primary end point was PFS Results: The study did not achieve its PFS end point (hazard ratio, 0.89; P = .23). The study was stopped when an early overall survival data analysis indicated an imbalance in total deaths favoring paclitaxel, predominantly in patients with high LDH levels. A prospectively defined subgroup analysis revealed a statistically significant improvement in median PFS for the combination in patients with normal baseline LDH Conclusion: The addition of elesclomol to paclitaxel did not significantly improve PFS in unselected patients with advanced melanoma. The association between baseline LDH and clinical outcomes suggests that LDH may be a predictive factor for treatment with this combination, consistent with recent findings on the association between elesclomol anticancer activity and cellular metabolic state.
AB - Purpose: Elesclomol, an investigational first-in-class compound, induces oxidative stress, triggers mitochondrial-induced apoptosis in cancer cells, and shows synergy with taxanes in tumor models. Following completion of a phase II trial of elesclomol in combination with paclitaxel that met its primary end point of progression-free survival (PFS), this randomized, double-blind, controlled phase III study was conducted to confirm the efficacy and tolerability of elesclomol in combination with paclitaxel versus paclitaxel alone in patients with advanced melanoma Patients and Methods: Patients with stage IV chemotherapy-naive melanoma (n = 651) were randomly assigned 1:1 to paclitaxel 80 mg/m2 either alone or in combination with elesclomol 213 mg/m2 administered weekly for 3 weeks of a 4-week cycle. Patients were stratified by prior systemic treatment, M1 subclass, and baseline lactate dehydrogenase (LDH) levels. The primary end point was PFS Results: The study did not achieve its PFS end point (hazard ratio, 0.89; P = .23). The study was stopped when an early overall survival data analysis indicated an imbalance in total deaths favoring paclitaxel, predominantly in patients with high LDH levels. A prospectively defined subgroup analysis revealed a statistically significant improvement in median PFS for the combination in patients with normal baseline LDH Conclusion: The addition of elesclomol to paclitaxel did not significantly improve PFS in unselected patients with advanced melanoma. The association between baseline LDH and clinical outcomes suggests that LDH may be a predictive factor for treatment with this combination, consistent with recent findings on the association between elesclomol anticancer activity and cellular metabolic state.
UR - http://www.scopus.com/inward/record.url?scp=84875980910&partnerID=8YFLogxK
U2 - 10.1200/JCO.2012.44.5585
DO - 10.1200/JCO.2012.44.5585
M3 - Article
C2 - 23401447
AN - SCOPUS:84875980910
SN - 0732-183X
VL - 31
SP - 1211
EP - 1218
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -